Human genetic similarity explained

Induced pluripotent stem cells from bonobos. Skin cells from bonobos, or pygmy chimps, were reprogrammed to IPS cells, an advance that allows scientists to study the differences between their and human neurons. The colors show different aspects of the cells' molecular components.
— Carol Marchetto, Salk Institute

Induced pluripotent stem cells from bonobos. Skin cells from bonobos, or pygmy chimps, were reprogrammed to IPS cells, an advance that allows scientists to study the differences between their and human neurons. The colors show different aspects of the cells' molecular components.
/ Carol Marchetto, Salk Institute

Despite superficial differences, human beings are very similar genetically, compared with our close relatives, chimpanzees and other great apes. Yet we have all been evolving for the same time since the last common ancestor.

That genetic similarity is one of human evolution’s deep mysteries. Did it happen by pure chance, or is it part of what makes us human? A new study led by scientists from the Salk Institute sheds light on how that came to be. And a study author says humanity’s genetic closeness may be necessary for civilization itself.

The study points to a genomic parasite that copies itself and spreads throughout the genome, disrupting it with mutations. Humans suppress that parasite much more effectively than their closest relatives, chimpanzees and pygmy chimps, or bonobos. And that has helped humans remain very similar to each other throughout the millions of years since we parted company with our ape ancestors.

The study was published Wednesday in the journal Nature.

Greg Wray, an evolutionary anthropologist at Duke University in North Carolina, said the study’s result was surprising, and that he is looking forward to more detailed examination of the genetic differences.

“Can we begin to connect those differences to things that are uniquely human — the things that make us distinctive as a species?” Wray asked.

Humans have a remarkable capability for languages and other features of civilized society, said Fred Gage, a Salk Institute researcher and senior author of the study. They have what researchers call a “theory of mind” — they can imagine how others think, and empathize with them. Animals don’t have this ability to nearly the same degree. It is a defining feature of humanity.

“This facilitates the transfer of cultural information,” Gage said. “I’m aware of your mind, and this is something chimps would have a tough time doing.”

If the genetic parasite were more active, it could have introduced major mutations, disrupting this highly advanced capability, Gage said.

The genomic parasite, called L1, exists only for itself. It’s part of a group of genetic elements called transposons, or jumping genes, that cut-and-paste themselves to other places in the genome. They do so not to help the individual, but because they can. For that reason, they’re sometimes called “selfish DNA.”

Most of these mobile elements actually can’t jump because they have been disabled by mutations, Gage said. But they are similar to sequences in other animals, presumably having been inherited from a common ancestor.

“More than 50 percent of your genome is made up of the residual elements that jumped around,” before being disabled by mutations, Gage said.

Just how this similarity got established is unclear, Gage said. Previous studies point to a “bottleneck” in the ancestral population, reducing the total numbers to just a few thousand.

The bottleneck could have been caused by an outbreak of disease, or environmental factors.

“You can imagine a locking-in process,” Wray said. “So some changes happen and we have a nice set of adaptations, then the jumping dials down, and we get to keep ’em. That’s one way to look at it. This study doesn’t actually show that, but it sets that up as a possibility, which is something people had not been directly thinking about before.”

Researchers studied the genomic differences by generating so-called induced pluripotent stem cells from chimps and bonobos, the first time this has been done, Gage said. The IPS cells can be studied alongside those of their human relatives.

IPS cells act like embryonic stem cells, and can be grown into nearly any cell in the body. This plasticity enables scientists to generate cells like neurons, otherwise hard to come by due to ethical restrictions on research.

Gage said these chimpanzee and bonobo IPS cells will be made available to other researchers.

Wray said he’s looking forward to getting those cells.

“The real potential for these cells is that they’re going to open up an entirely new line of inquiry into how we study the genetic basis for disease,” Wray said. “We as a species get diseases that are different or have different outcomes than chimpanzees or bonobos. This is a great way to study that, because we can manipulate those cells. We can culture them under different conditions, expose them to certain pathogens, knock out certain genes, see how they react and understand the molecular mechanisms of disease.”

The next step is to produce more IPS cells from other great apes and from monkeys, and from more people, Gage said.